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Choose BLINCYTO® as a treatment option for pediatric and AYA patients with CD19-positive B-cell precursor ALL in frontline consolidation and those with R/R disease1

MT103-205, the pivotal study of BLINCYTO® in pediatric patients with R/R B-cell precursor ALL: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in 70 patients < 18 years of age with B-cell precursor ALL and > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70; 95% CI: 22.1–45.1).1,2,†

Learn more about the MT103-205 pivotal study

†CR was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and full recovery of peripheral blood counts (platelets > 100,000/µL and ANC > 1,000/µL). CRh* was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and partial recovery of peripheral blood counts (platelets > 50,000/µL and ANC > 500/µL).1

Study design: A randomized, controlled, open-label, phase 3 study of BLINCYTO® vs chemotherapy in 111 patients 28 days to 18 years of age with high-risk,* first-relapsed, Ph(–) B-cell precursor ALL with < 25% blasts in the bone marrow after induction and 2 cycles of consolidation chemotherapy.† Patients were randomized to receive BLINCYTO®‡ or the IntReALL HR 2010 HC3 intensive combination chemotherapy§ as the third cycle of consolidation. Patients were to proceed to HSCT after this cycle of consolidation. Efficacy was established on the basis of OS and RFS. 5-year KM estimates for OS were 78.4% in the BLINCYTO® arm (n=54) vs 41.4% in the chemotherapy only arm (n=57); HR: 0.35 (95% CI: 0.17–0.70). 5-year KM estimates for RFS were 61.1% in the BLINCYTO® arm (n=54) vs 27.6% in the chemotherapy only arm (n=57); HR: 0.38 (95% CI: 0.22–0.66).1

*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.3

†Induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.4

‡Patients in the BLINCYTO® arm received one cycle of BLINCYTO® as a continuous IV infusion at 15 mcg/m2/day over 4 weeks (maximum daily dose was not to exceed 28 mcg/day).1

§Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.3,5

BLINCYTO® efficacy was established based on OS and RFS vs chemotherapy in pediatric and AYA patients with B-cell precursor ALL in high-risk first relapse1

OS for BLINCYTO® vs chemotherapy1

OS for BLINCYTO® (blinatumomab) vs chemotherapy

OS for BLINCYTO® (blinatumomab) vs chemotherapy

  • The median follow-up time for OS was 55.2 months for the overall population1

RFS for BLINCYTO® vs chemotherapy1

RFS for BLINCYTO® (blinatumomab) vs chemotherapy

*Months were calculated as days from randomization date to event/censor date, divided by 30.5.1
†The hazard ratio estimates are obtained from the Cox proportional hazard model.1

ALL, acute lymphoblastic leukemia; ANC, absolute neutrophil count; AYA, adolescent and young adult; BM, bone marrow; CD, cluster of differentiation; CI, confidence interval; CR, complete remission; CRh*, complete remission with partial hematologic recovery; EM, extramedullary; HC1, high-risk consolidation block 1; HC2, high-risk consolidation block 2; HC3, high-risk consolidation block 3; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IV, intravenous; KM, Kaplan-Meier; OS, overall survival; Ph(–), Philadelphia chromosome–negative; RFS, relapse-free survival; R/R, relapsed or refractory.

Amgen 20120215 study design and baseline characteristics of patients

Patients 28 days to 18 years of age with Ph(–) B-cell precursor ALL in high-risk first relapse1,4,*

Reinduction chemotherapy followed by 2 cycles of consolidation chemotherapy†
1:1
Randomization
1
1
BLINCYTO® consolidation (n=54)
•One cycle of BLINCYTO® (15 mcg/m2/day for 28 days)
Chemotherapy consolidation (n=57)
•IntReALLHR2010 HC3 intensive combination chemotherapy‡
HSCT
Reinduction chemotherapy followed by 2 cycles of consolidation chemotherapy†
1:1
Randomization
1
1
BLINCYTO®
consolidation (n=54)
•One cycle of BLINCYTO® (15 mcg/m2/day for 28 days)
Chemotherapy consolidation (n=57)
•IntReALLHR2010 HC3 intensive combination chemotherapy‡
HSCT

Endpoints:1

  • OS
  • RFS
Key inclusion criteria1
Ph(–) B-cell precursor ALL in high-risk first relapse
< 25% blasts in the BM
Key exclusion criteria6
Clinically relevant CNS pathology requiring treatment
Evidence of current CNS (CNS2, CNS3) involvement by ALL§
Abnormal renal or hepatic function prior to start of treatment

Demographics and baseline characteristics1

Characteristic BLINCYTO ®
(n=54) 		Chemotherapy
(n=57)
Age, n (%)
Median, (range) 6 (1, 17) 5 (1, 17)
< 1 year 0 0
1 to 9 years 39 (72) 41 (72)
≥ 10 to 18 years 15 (28) 16 (28)
Sex, n (%)
Males, n (%) 30 (56) 23 (40)
Race, n (%)
American Indian or
Alaska Native 		0 0
Asian 1 (2) 3 (5)
Black (or African American) 0 3 (5)
Native Hawaiian or Other Pacific Islander 0 0
Other 3 (6) 5 (9)
White 50 (93) 46 (81)
Cytomorphology at randomization, n (%)
Blasts < 5% 54 (100) 54 (95)
Blasts ≥ 5% and < 25% 0 2 (4)
Blasts ≥ 25% 0 0
Not evaluable 0 1 (2)
MRD PCR value at randomization, n (%)
≥ 10-3 11 (20) 16 (28)
< 10-3 and ≥ 10-4 15 (28) 6 (11)
< 10-4 20 (37) 23 (40)
Unknown 8 (15) 12 (21)
Time from first diagnosis to relapse (month), n (%)
< 18 months 19 (35) 22 (39)
≥ 18 months and ≤ 30 months 32 (59) 31 (54)
> 30 months 3 (6) 4 (7)

*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.3

†Induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.4

‡Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.3,5

§CNS2, patients with WBC count in CSF < 5 per microliter and having blasts in the CSF; CNS3, patients with WBC count in CSF ≥ 5 per microliter and having blasts in the CSF, or clinical/radiographic signs of central nervous leukemia.7

CNS, central nervous system; CSF, cerebrospinal fluid; MRD, measurable or minimal residual disease; PCR, polymerase chain reaction; WBC, white blood cell.

See the full safety profile of the Amgen 20120215 study

Learn more

Study design: A randomized, controlled, open-label, phase 3 study of patients 1–27 years of age with Ph(–) B-cell precursor ALL in first relapse.8

  • Patients in high-risk (HR)* or intermediate-risk (IR)† first relapse: Following one UKALLR3 reinduction chemotherapy block, patients were randomized to receive cycles 1 and 2 of BLINCYTO® (n=105) as post-reinduction consolidation therapy or blocks 2 and 3 of consolidation chemotherapy (n=103) based on the UKALLR3 trial.‡ The primary endpoint was DFS: 54% at 2 years for patients receiving BLINCYTO® vs 39% for patients receiving chemotherapy; P = 0.03; HR: 0.70 (95% CI: 0.47-1.03). The difference was not statistically significant8
  • Patients in low-risk (LR)§ first relapse: Following one UKALLR3 reinduction chemotherapy block, patients were randomized to receive 3 cycles of BLINCYTO® alternating with chemotherapy (n=127) or chemotherapy alone (n=128), modified from the UKALLR3 regimen. The primary endpoint was DFS : 61.2% at 4 years for patients receiving chemotherapy alternating with BLINCYTO® vs 49.5% for patients receiving chemotherapy alone; 1-sided P = 0.089; HR: 0.76 (95% CI: 0.51–1.14)9
  • Dosing of BLINCYTO® was 15 mcg/m2/day for 28 days, then 7 days off. Premedication with 5 mg/m2/dose of dexamethasone was administered before the first cycle of BLINCYTO®7,9

*Patients who had an iBM or combined BM + EM relapse < 36 months after diagnosis or who had an iEM relapse < 18 months after diagnosis were assigned to the high-risk group.8

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months after diagnosis or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8

‡UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,10

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.8

ALL, acute lymphoblastic leukemia; BM, bone marrow; CI, confidence interval; COG, Children's Oncology Group; DFS, disease-free survival; EM, extramedullary; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IT, intrathecal; IV, intravenous; MRD, measurable or minimal residual disease; OS, overall survival; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory.

BLINCYTO® efficacy was established based on DFS and OS vs chemotherapy in pediatric and AYA patients with B-cell precursor ALL in first relapse8,9

IR* and HR† relapse

2-year DFS for BLINCYTO® vs chemotherapy8

(HR: 0.70 [95% CI: 0.47–1.03]; P = 0.03)‡

‡The difference was not statistically significant.8

OS for BLINCYTO® vs chemotherapy8

2-year OS for BLINCYTO® (blinatumomab) vs chemotherapy

OS for BLINCYTO® vs chemotherapy

  • Median follow-up was 2.9 years8

*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.8

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8

LR§ relapse

  • The 4-year DFS rate was 61.2% ± 5.0% in the BLINCYTO® arm and 49.5% ± 5.2% in the chemotherapy arm (HR: 0.76; 95% CI: 0.51–1.14; 1-sided P = 0.089). The difference was not statistically significant9
  • Median follow-up was 3.5 years9

§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction. 8

AYA, adolescent and young adult.

COG AALL1331 study design and baseline characteristics of patients

Patients 1–27 years of age with Ph(–) B-cell precursor ALL in first relapse7-11

BLINCYTO® (blinatumomab) consolidation

  • HR* and IR† study schematic

    BLINCYTO® (blinatumomab) consolidation BLINCYTO® (blinatumomab) consolidation

  • LR§ study schematic

    BLINCYTO® (blinatumomab) consolidation BLINCYTO® (blinatumomab) consolidation

Endpoints for HR/IR analysis:8

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
  • Exploratory endpoint: MRD response
  • Post hoc endpoint: Ability to proceed to HSCT

Endpoints for LR analysis:8,9

  • Primary endpoint: Disease-free survival
  • Secondary endpoint: Overall survival
Key inclusion criteria8
B-cell precursor ALL in first relapse
Key exclusion criteria8
Down syndrome
Ph(+) B-cell precursor ALL
Previous HSCT or BLINCYTO® treatment
Enrollment was terminated early in the HR and IR groups due to encouraging efficacy and lower rates of serious toxicity in the BLINCYTO® arm vs chemotherapy, based on a recommendation from the Independent Data Safety Monitoring Committee8

BLINCYTO® was evaluated in pediatric and AYA patients in first relapse8

Baseline characteristics of patients in HR or IR first relapse8

BLINCYTO ®
(n=105)
n (%) 		Chemotherapy
(n=103)
n (%)
Age at enrollment (years)
Median (interquartile range) 		9 (6–16) 9 (5–16)
1–9 55 (52.4) 55 (53.4)
10–12 10 (9.5) 11 (10.7)
13–17 25 (23.8) 19 (18.4)
18–20 8 (7.6) 10 (9.7)
21–27 7 (6.7) 8 (7.8)
Sex
Female 48 (45.7) 49 (47.6)
Male 57 (54.3) 54 (52.4)
Risk group assignment after reinduction
High risk* 69 (65.7) 69 (67.0)
Intermediate risk† 36 (34.3) 34 (33.0)
Cytogenetic group at diagnosis
Favorable
ETV6-RUNX1, No.
Hyperdiploid with +4, +10, No. 		21 (23.3)
12
9 		16 (17.6)
8
8
Unfavorable
KMT2A-rearranged, No.
Hypodiploid, No. 		7 (7.8)
7
0 		10 (11.0)
9
1
Other
Unknown, No. 		62 (68.9)
15		 65 (71.4)
12
 

*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.8

†Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8

§UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,10

‡Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.8

HR, high risk; IR, intermediate risk; Ph(+), Philadelphia chromosome–positive.

See the safety results of BLINCYTO® vs chemotherapy in COG AALL1331 in HR or IR first relapse

Learn more

Study design: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in patients < 18 years of age with > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70); (95% CI: 22.1–45.1).1,2

About a third of all patients achieved CR/CRh* within the first 2 cycles of BLINCYTO®1

Primary endpoint was CR/CRh* in the first 2 cycles1,†

Within the First Two Treatment Cycles of BLINCYTO®

Within the first two treatments of BLINCYTO® (blinatumomab) 33% of patients achieved CR/CRh Within the first two treatments of BLINCYTO® (blinatumomab) 33% of patients achieved CR/CRh
  • 73.9% of CR/CRh* occurred in cycle 1 (n=17/23)1
  • 26.1% of CR/CRh* occurred in cycle 2 (n=6/23)1

†CR was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and full recovery of peripheral blood counts (platelets > 100,000/μL and ANC > 1,000/μL). CRh* was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and partial recovery of peripheral blood counts (platelets > 50,000/µl and ANC > 500/µl).1

ANC, absolute neutrophil count; BM, bone marrow; CI, confidence interval; CR, complete remission; CRh*, complete remission with partial hematologic recovery; HSCT, allogeneic hematopoietic stem cell transplantation; NCCN, National Comprehensive Cancer Network; R/R, relapsed or refractory.

MT103-205 study design and baseline characteristics of patients

  • MT103-205 study design: An international, open-label, single-arm, phase 1/2 study1

BLINCYTO® was studied as a single-agent therapy via continuous IV infusion2

  • Phase 1: Dose finding
  • Phase 2:
    • Dosage: 5/15 mcg/m2/day (5 mcg/m2/day for the first week of the first cycle followed by 15 mcg/m2/day thereafter)
    • Treatment cycle: 4 weeks on treatment, 2 weeks off
Key inclusion criteria2
Primary refractory disease
First relapse after full salvage induction
Second or later relapse, or in any relapse after HSCT
Age < 18 years
KPS ≥ 50% or LPS ≥ 50% for patients < 16 years of age
Key exclusion criteria2
Active acute or extensive chronic GvHD after HSCT
Evidence of active CNS involvement
Evidence of active testicular involvement
MT103-205 included heavily pretreated pediatric patients2

Baseline Characteristics (N=70)2,*

Sex, n (%)
Male 47 (67)
Age, n (%)
< 2 years 10 (14)
2–6 years 20 (29)
7–17 years 40 (57)
Previous relapses, n (%)
0 (primary refractory disease) 2 (3)
1 31 (44)
2 29 (41)
≥ 3 8 (11)
Previous HSCT, n (%) 40 (57)
Baseline BM blasts, n (%)
< 50% 18 (26)
≥ 50% 52 (74)

*All patients treated at the stepwise dosage of 5 or 15 mcg/m2/day in phase 1 or phase 2.2

BM, bone marrow; CNS, central nervous system; GvHD, graft versus host disease; HSCT, allogeneic hematopoietic stem cell transplantation; IV, intravenous; KPS, Karnofsky performance status; LPS, Lansky performance status.

MRD(+): Retrospective study

BLAST, the pivotal study of BLINCYTO® in adult patients with MRD(+) B-cell precursor ALL: N=86, an open-label, single-arm phase 2 study of adult patients with MRD(+) B-cell precursor ALL who had received at least 3 chemotherapy blocks of standard ALL therapy, were in hematologic complete remission (defined as < 5% blasts in bone marrow, absolute neutrophil count > 1 Gi/L, platelets > 100 Gi/L), and had MRD* at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%. Primary endpoint: 81% (n=70/86) of patients had no detectable MRD assessed after 1 treatment cycle with BLINCYTO®1,12,*

In a retrospective study (Keating, et al), nearly all pediatric patients on BLINCYTO® achieved MRD negativity and subsequently proceeded to allogeneic hematopoietic stem cell transplantation (HSCT).13

A multi-institutional, retrospective study to report outcomes using BLINCYTO® as therapy prior to HSCT13

  • Pediatric patients (N=15) aged 0–21 years with MRD(+) B-cell precursor ALL13,†
  • All patients were in CR‡ at enrollment13
    • Two-thirds of the patients (10/15) were in CR1 and one-third (5/15) were in CR2
  • More than half of patients (9/15) had unfavorable risk cytogenetic abnormalities13
  • 93% (n=14/15) of patients had no detectable MRD following BLINCYTO® therapy13
  • Median time from end of BLINCYTO® treatment to preparative regimen for HSCT was 14 days (range: 1–35 days)13
    • All patients had successful neutrophil engraftment with a median time of 19 days (range: 11–35 days)
  • There are ongoing trials investigating BLINCYTO® in MRD(+) patients14

*Defined as the absence of detectable MRD confirmed in an assay with minimum sensitivity of 0.01% for 6 patients and ≤ 0.005% for 80 patients. Undetectable MRD was achieved by 65 of 80 patients with an assay sensitivity of at least 0.005%.1

†Most patients (n=12) received a single 4-week course of BLINCYTO® at 15 mcg/m2/day; 2 patients had their initial cycle of BLINCYTO® shortened to start HSCT preparative therapy (at days 18 and 20), and 1 patient received 2 courses for a total of 66 days.13

‡Defined as < 5% blasts in the bone marrow.13

ALL, acute lymphoblastic leukemia; CR1, first complete remission; CR2, second complete remission; CR, complete remission; MRD, measurable or minimal residual disease; NCCN, National Comprehensive Cancer Network; R/R, relapsed or refractory.

NCCN Recommended
NCCN Recommended

Frontline consolidation and R/R: According to the National Comprehensive Cancer Network® (NCCN®) for Pediatric ALL recommend blinatumomab as a treatment option across lines of therapy in pediatric patients with B-cell precursor ALL with:15

  • Ph(–) disease in frontline consolidation regardless of MRD status
  • Relapsed or refractory disease

See more

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications

BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions
  • Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin, and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome (CLS), and hemophagocytic histiocytosis/macrophage activation syndrome (MAS). Using all of these terms to define CRS in clinical trials of BLINCYTO®, CRS was reported in 15% of patients with R/R ALL, in 7% of patients with MRD-positive ALL, and in 16% of patients receiving BLINCYTO® cycles in the consolidation phase of therapy. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
  • Neurological Toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome: BLINCYTO® can cause serious or life-threatening neurologic toxicity, including ICANS. The incidence of neurologic toxicities in clinical trials was approximately 65%. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Grade 3 or higher neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. The majority of neurologic toxicities resolved following interruption of BLINCYTO®, but some resulted in treatment discontinuation.

    The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. There is limited experience with BLINCYTO® in patients with active ALL in the central nervous system (CNS) or a history of neurologic events. Patients with a history or presence of clinically relevant CNS pathology were excluded from clinical studies. Patients with Down Syndrome over the age of 10 years may have a higher risk of seizures with BLINCYTO® therapy.

    Monitor patients for signs and symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO® as outlined in the PI. Advise outpatients to contact their healthcare professional if they develop signs or symptoms of neurological toxicities.

  • Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed.
  • Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events.
  • Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs.
  • Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures and ICANS, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered.
  • Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and total blood bilirubin prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if total bilirubin rises to > 3 times ULN.
  • Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed.
  • Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
  • Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
  • Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®.
  • Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the “gasping syndrome,” have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.

    Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.

    Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

  • Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO® and for 48 hours after the last dose.
Adverse Reactions
  • The safety of BLINCYTO® in adult and pediatric patients one month and older with MRD-positive B-cell precursor ALL (n=137), relapsed or refractory B-cell precursor ALL (n=267), and Philadelphia chromosome-negative B-cell precursor ALL in consolidation (n=165) was evaluated in clinical studies. The most common adverse reactions (≥ 20%) to BLINCYTO® in this pooled population were pyrexia, infusion-related reactions, headache, infection, musculoskeletal pain, neutropenia, nausea, anemia, thrombocytopenia, and diarrhea.
Dosage and Administration Guidelines
  • BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
  • It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
INDICATIONS

BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:

  • Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy
  • Minimal residual disease (MRD) greater than or equal to 0.1% in first or second complete remission
  • Relapsed or refractory disease

Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.

BLINCYTO® is a registered trademark of Amgen Inc.

References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34:4381-4389. 3. Data on file, Amgen; 2020. 4. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:843-854. 5. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl 3):843-854. 6. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl):843-854. 7. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl 2):833-842. 8. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:833-842. 9. Hogan LE, Brown PA, Ji L, et al. Children’s Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol. 2023. doi:10.1200/JCO.22.02200. 10. Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomized trial. Lancet. 2010;376:2009-2017. 11. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl):833-842. 12. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131:1522-1531. 13. Keating AK, Gossai N, Phillips CL, et al. Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Adv. 2019;3:1926-1929. 14. ClinicalTrials.gov. https://classic.clinicaltrials.gov/ct2/results?term=blinatumomab&cond=Residual+Disease%2C+Minimal&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=Intr&rslt=&Search=Apply. Accessed July 16, 2024. 15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.1.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 3, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

  • Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended.
  • Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended.
Contraindications
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